{"doi":"10.1083/jcb.202110114","title":"Type II phosphatidylinositol 4-kinases function sequentially in cargo delivery from early endosomes to melanosomes","abstract":"Melanosomes are pigment cell-specific lysosome-related organelles in which melanin pigments are synthesized and stored. Melanosome maturation requires delivery of melanogenic cargoes via tubular transport carriers that emanate from early endosomes and that require BLOC-1 for their formation. Here we show that phosphatidylinositol-4-phosphate (PtdIns4P) and the type II PtdIns-4-kinases (PI4KIIα and PI4KIIβ) support BLOC-1-dependent tubule formation to regulate melanosome biogenesis. Depletion of either PI4KIIα or PI4KIIβ with shRNAs in melanocytes reduced melanin content and misrouted BLOC-1-dependent cargoes to late endosomes/lysosomes. Genetic epistasis, cell fractionation, and quantitative live-cell imaging analyses show that PI4KIIα and PI4KIIβ function sequentially and non-redundantly downstream of BLOC-1 during tubule elongation toward melanosomes by generating local pools of PtdIns4P. The data show that both type II PtdIns-4-kinases are necessary for efficient BLOC-1-dependent tubule elongation and subsequent melanosome contact and content delivery during melanosome biogenesis. The independent functions of PtdIns-4-kinases in tubule extension are downstream of likely redundant functions in BLOC-1-dependent tubule initiation.","journal":"The Journal of Cell Biology","year":2022,"id":256834,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":19,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9586,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":830943,"name":"Shuixing Li","orcid":"0000-0003-2679-7655","position":1,"is_corresponding":false},{"id":686548,"name":"Alexa Jaume","orcid":"0000-0001-8218-6635","position":2,"is_corresponding":false},{"id":457277,"name":"Riddhi Atul Jani","orcid":"0000-0002-0068-2166","position":3,"is_corresponding":false},{"id":293061,"name":"Cédric Delevoye","orcid":"0000-0002-3835-6649","position":4,"is_corresponding":false},{"id":615650,"name":"Graça Raposo","orcid":"0000-0001-9590-1298","position":5,"is_corresponding":false},{"id":274300,"name":"Michael S. Marks","orcid":"0000-0001-7435-7262","position":6,"is_corresponding":false},{"id":376680,"name":"Yueyao Zhu","orcid":"0000-0001-6358-4996","position":0,"is_corresponding":true}],"reference_count":80,"raw_metadata":null,"created_at":"2026-07-19T00:25:25.728895Z","pmid":"36169639","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}